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Identification
NameDaclizumab
Accession NumberDB00111  (BTD00007, BIOD00007)
TypeBiotech
GroupsApproved, Investigational
Description

Humanized IgG1 Mab that binds to the human interleukin-2 receptor (anti-Tac or anti-CD25). Daclizumab is a composite of human (90%) and murine (10%) antibody sequences. The human sequences were derived from the constant domains of human IgG1 and the variable framework regions of the Eu myeloma antibody. The murine sequences were derived from the complementarity-determining regions of a murine anti-Tac antibody.

Protein structureDb00111
Related Articles
Protein chemical formulaC6332H9808N1678O1989S42
Protein average weight142612.1 Da
Sequences
>Humanized Anti-CD25 Heavy Chain 1
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSYRMHWVRQAPGQGLEWIGYINPSTGYTEY
NQKFKDKATITADESTNTAYMELSSLRSEDTAVYYCARGGGVFDYWGQGTTLTVSSGPSV
FPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV
VTVPSSSLGTQTYICNVNHKPSNTKVDKKAEPKSCDKTHTCPPCPAPELLGGPSVFLFPP
KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV
LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL
TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGK
>Humanized Anti-CD25 Light Chain 1
DIQMTQSPSTLSASVGDRVTITCSASSSISYMHWYQQKPGKAPKLLIYTTSNLASGVPAR
FSGSGSGTEFTLTISSLQPDDFATYYCHQRSTYPLTFGSGTKVEVKRTVAAPSVFIFPPS
DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL
SKADYEKHKVYACEVTHQGLSSPVTKSFNR
Download FASTA Format
Synonyms
Anti-IL-2
Humanized antiCD25
Ig gamma-1 chain C region
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Zenapax 5mg/mlliquid5 mgintravenousHoffmann La Roche Limited2000-03-022011-10-17Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
ZenapaxHoffmann-La Roche Inc
Brand mixturesNot Available
SaltsNot Available
Categories
UNIICUJ2MVI71Y
CAS number152923-56-3
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Pharmacology
IndicationZenapax is a humanized monoclonal antibody used for prevention of renal transplant rejection
PharmacodynamicsZenapax functions as an IL-2 receptor antagonist. Specifically it inhibits IL-2-mediated activation of lymphocytes, a critical pathway in the cellular immune response involved in allograft rejection.
Mechanism of actionZenepax binds with high-affinity to the Tac subunit of the high-affinity IL-2 receptor complex and inhibits IL-2 binding. The IL-2 receptor (Tac) subunit is expressed on activated but not resting lymphocytes.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Most likely removed by opsonization via the reticuloendothelial system when bound to lymphocytes.

Route of eliminationNot Available
Half life11-38 days
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Liquidintravenous5 mg
PricesNot Available
PatentsNot Available
Properties
StateLiquid
Experimental Properties
PropertyValueSource
melting point61 °C (FAB fragment), 71 °C (whole mAb)Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000)
hydrophobicity-0.437Not Available
isoelectric point8.46Not Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesL04AC01
AHFS Codes
  • 92:00.00
PDB Entries
FDA labelDownload (666 KB)
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antibody
General Function:
Interleukin-2 receptor activity
Specific Function:
Receptor for interleukin-2. The receptor is involved in the regulation of immune tolerance by controlling regulatory T cells (TREGs) activity. TREGs suppress the activation and expansion of autoreactive T cells.
Gene Name:
IL2RA
Uniprot ID:
P01589
Molecular Weight:
30818.915 Da
References
  1. Shamsi TS, Irfan M, Farzana T, Ansari SH, Ahmad G, Shakoor N, Baig MI: Allogeneic peripheral blood stem cell transplant (PBSCT) using anti-IL2 receptor antibody Daclizumab for the prevention of acute graft versus host disease in steroid refractory Diamond Blackfan anaemia: a case report. J Pak Med Assoc. 2005 Oct;55(10):454-5. [PubMed:16304857 ]
  2. Przepiorka D, Kernan NA, Ippoliti C, Papadopoulos EB, Giralt S, Khouri I, Lu JG, Gajewski J, Durett A, Cleary K, Champlin R, Andersson BS, Light S: Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease. Blood. 2000 Jan 1;95(1):83-9. [PubMed:10607689 ]
  3. Garcia CD, Bittencourt VB, Tumelero A, Antonello JS, Malheiros D, Garcia VD: Plasmapheresis for recurrent posttransplant focal segmental glomerulosclerosis. Transplant Proc. 2006 Jul-Aug;38(6):1904-5. [PubMed:16908318 ]
  4. Krouwels FH, van der Heijden JF, Lutter R, van Neerven RJ, Jansen HM, Out TA: Glucocorticosteroids affect functions of airway- and blood-derived human T-cell clones, favoring the Th1 profile through two mechanisms. Am J Respir Cell Mol Biol. 1996 Apr;14(4):388-97. [PubMed:8600944 ]
  5. Patlolla V, Zhong X, Reed GW, Mandelbrot DA: Efficacy of anti-IL-2 receptor antibodies compared to no induction and to antilymphocyte antibodies in renal transplantation. Am J Transplant. 2007 Jul;7(7):1832-42. [PubMed:17564638 ]
  6. Monti P, Brigatti C, Heninger AK, Scirpoli M, Bonifacio E: Disengaging the IL-2 receptor with daclizumab enhances IL-7-mediated proliferation of CD4(+) and CD8(+) T cells. Am J Transplant. 2009 Dec;9(12):2727-35. doi: 10.1111/j.1600-6143.2009.02825.x. Epub 2009 Sep 25. [PubMed:19788505 ]
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antibody
General Function:
Interleukin-2 receptor activity
Specific Function:
Receptor for interleukin-2. This beta subunit is involved in receptor mediated endocytosis and transduces the mitogenic signals of IL2.
Gene Name:
IL2RB
Uniprot ID:
P14784
Molecular Weight:
61116.59 Da
References
  1. Light JA, Sasaki TM, Ghasemian R, Barhyte DY, Fowlkes DL: Daclizumab induction/tacrolimus sparing: a randomized prospective trial in renal transplantation. Clin Transplant. 2002;16 Suppl 7:30-3. [PubMed:12372041 ]
  2. Aguillon JC, Contreras J, Dotte A, Cruzat A, Catalan D, Salazar L, Molina MC, Guerrero J, Lopez M, Soto L, Salazar-Onfray F, Cuchacovich M: [New immunological weapons for medicine in the 21st Century: biological therapy based on the use of the latest generation monoclonal antibodies]. Rev Med Chil. 2003 Dec;131(12):1445-53. [PubMed:15022409 ]
  3. Forrest K, Logan B, Strange J, Roszman TL, Goebel J: Daclizumab therapy in kidney transplantation-different mechanisms of action in- versus ex-vivo? Transpl Immunol. 2005 Mar;14(1):43-7. Epub 2005 Jan 4. [PubMed:15814281 ]
  4. Ramos EL, Milford EL, Kirkman RL, Tilney NL, Strom TB, Shapiro ME, Waldmann TA, Wood IG, Rollins MR, Carpenter CB: Differential IL-2 receptor expression in renal allograft recipients treated with an anti-IL-2-receptor antibody. Transplantation. 1989 Sep;48(3):415-20. [PubMed:2571203 ]
  5. Burkhardt K, Mandel TE, Diamantstein T, Loughnan MS: Anti-IL-2 receptor monoclonal antibody AMT-13 increases soluble IL-2 receptor levels in vivo. Immunology. 1989 Feb;66(2):183-9. [PubMed:2647626 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Not Available
Specific Function:
Receptor for the Fc region of immunoglobulins gamma. Low affinity receptor. Binds complexed or aggregated IgG and also monomeric IgG. Contrary to III-A, is not capable to mediate antibody-dependent cytotoxicity and phagocytosis. May serve as a trap for immune complexes in the peripheral circulation which does not activate neutrophils.
Gene Name:
FCGR3B
Uniprot ID:
O75015
Molecular Weight:
26215.64 Da
References
  1. Hoshino S, Oshimi K, Teramura M, Mizoguchi H: Activation via the CD3 and CD16 pathway mediates interleukin-2-dependent autocrine proliferation of granular lymphocytes in patients with granular lymphocyte proliferative disorders. Blood. 1991 Dec 15;78(12):3232-40. [PubMed:1835892 ]
  2. Martelletti P, Stirparo G, De Stefano L, Di Sabato F, Giacovazzo M, Rinaldi-Garaci C: Defective expression of IL-2 receptors on peripheral blood lymphocytes from patients with cluster headache. Headache. 1990 Mar;30(4):228-31. [PubMed:2335478 ]
  3. Galandrini R, Albi N, Tripodi G, Zarcone D, Terenzi A, Moretta A, Grossi CE, Velardi A: Antibodies to CD44 trigger effector functions of human T cell clones. J Immunol. 1993 May 15;150(10):4225-35. [PubMed:8097750 ]
  4. Lanier LL, Kipps TJ, Phillips JH: Functional properties of a unique subset of cytotoxic CD3+ T lymphocytes that express Fc receptors for IgG (CD16/Leu-11 antigen). J Exp Med. 1985 Dec 1;162(6):2089-106. [PubMed:2415663 ]
  5. Hayakawa K, Salmeron MA, Kornbluth J, Bucana C, Itoh K: The role of IL-4 in proliferation and differentiation of human natural killer cells. Study of an IL-4-dependent versus an IL-2-dependent natural killer cell clone. J Immunol. 1991 Apr 1;146(7):2453-60. [PubMed:1900882 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Serine-type peptidase activity
Specific Function:
C1r B chain is a serine protease that combines with C1q and C1s to form C1, the first component of the classical pathway of the complement system.
Gene Name:
C1R
Uniprot ID:
P00736
Molecular Weight:
80118.04 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Not Available
Specific Function:
C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes.
Gene Name:
C1QA
Uniprot ID:
P02745
Molecular Weight:
26016.47 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Not Available
Specific Function:
C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes.
Gene Name:
C1QB
Uniprot ID:
P02746
Molecular Weight:
26721.62 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Not Available
Specific Function:
C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes.
Gene Name:
C1QC
Uniprot ID:
P02747
Molecular Weight:
25773.56 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Not Available
Specific Function:
Receptor for the Fc region of IgG. Binds complexed or aggregated IgG and also monomeric IgG. Mediates antibody-dependent cellular cytotoxicity (ADCC) and other antibody-dependent responses, such as phagocytosis.
Gene Name:
FCGR3A
Uniprot ID:
P08637
Molecular Weight:
29088.895 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Receptor signaling protein activity
Specific Function:
High affinity receptor for the Fc region of immunoglobulins gamma. Functions in both innate and adaptive immune responses.
Gene Name:
FCGR1A
Uniprot ID:
P12314
Molecular Weight:
42631.525 Da
References
  1. Simms HH, Gaither TA, Fries LF, Frank MM: Monokines released during short-term Fc gamma receptor phagocytosis up-regulate polymorphonuclear leukocytes and monocyte-phagocytic function. J Immunol. 1991 Jul 1;147(1):265-72. [PubMed:1828823 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Not Available
Specific Function:
Binds to the Fc region of immunoglobulins gamma. Low affinity receptor. By binding to IgG it initiates cellular responses against pathogens and soluble antigens. Promotes phagocytosis of opsonized antigens.
Gene Name:
FCGR2A
Uniprot ID:
P12318
Molecular Weight:
35000.42 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Not Available
Specific Function:
Receptor for the Fc region of complexed or aggregated immunoglobulins gamma. Low affinity receptor. Involved in a variety of effector and regulatory functions such as phagocytosis of immune complexes and modulation of antibody production by B-cells. Binding to this receptor results in down-modulation of previous state of cell activation triggered via antigen receptors on B-cells (BCR), T-cells ...
Gene Name:
FCGR2B
Uniprot ID:
P31994
Molecular Weight:
34043.355 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Transmembrane signaling receptor activity
Specific Function:
Receptor for the Fc region of complexed immunoglobulins gamma. Low affinity receptor. Involved in a variety of effector and regulatory functions such as phagocytosis of immune complexes and modulation of antibody production by B-cells.
Gene Name:
FCGR2C
Uniprot ID:
P31995
Molecular Weight:
35577.96 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23